COC plus spironolactone more effective than metformin for PCOS
In women with polycystic ovary syndrome (PCOS), combined oral contraceptive (COC) with spironolactone is more effective than metformin in reducing symptoms while showing a similar safety profile, according to a new randomized clinical trial (RCT).
“In our present RCT, the combination of COC plus spironolactone was more effective than metformin for the treatment of PCOS in terms of amelioration of clinical and biochemical hyperandrogenism and restoration of regular menstrual bleeding,” researchers said.
The researchers randomized 46 women with classic PCOS to receive either metformin (n=22; mean age 23±6 years; mean body mass index [BMI], 312.2±9.0 kg/m2) or COC plus spironolactone (n=24; mean age 25±5 years; mean BMI, 30.6±7.9 kg/m2). There were no significant differences in baseline characteristics between the treatment groups.
Compared with metformin, COC plus spironolactone produced a significant reduction in hirsutism score (mean difference [MD], 4.6 points; 95 percent CI, 2.6 to 6.7 points; p<0.0001) and total testosterone (MD, 1.1 nmol/L; 0.4 to 1.7 nmol/L; p<0.0001). [Eur J Endocrinol 2017;177:399-408]
Reductions in free testosterone (MD, 25 pmol/L; 12 to 39 pmol/L; p=0.0002), androstenedione (MD, 5.5 nmol/L; 1.8 to 9.2 nmol/L; p=0.0002) and dehydroepiadrosterone-sulphate (DHEAS; MD, 2.7 µmol/L; 1.4 to 4.0 µmol/L; p<0.0001) were also significantly greater in women who received COC plus spironolactone.
In contrast, DHEAS levels in those who took metformin increased by 35 percent.
There was also a lower frequency of menstrual dysfunction in the group who took COC plus spironolactone compared with those who took metformin (odds ratio [OR], 0.06; 0.02 to 0.23; p<0.0001).
There were no differences in the frequencies of cardiometabolic disorders such as abnormal glucose tolerance (OR, 1.7; 0.7 to 4.4; p=0.255), dyslipidaemia (OR, 0.6; 0.2 to 1.8; p=0.390) and hypertension (OR, 0.3; 0.5 to 2.0; p=0.219).
Current findings indicate that, despite the recent popularity of insulin sensitizers such as metformin, the traditional approach of using COC and antiandrogens appears to have higher efficacy and result in fewer negative side-effects, according to researchers.
COCs are thought to worsen insulin resistance and glucose tolerance which is detrimental to PCOS patients who frequently also have insulin resistance and other metabolic comorbidities, explained researchers. This contributed greatly to the increase in preference for insulin sensitizers.
“However, our present results provide evidence that when associated with lifestyle advice, COC plus spironolactone did not appear to influence negatively the metabolic milieu of PCOS, showing no overall differences with metformin on surrogate indexes of insulin resistance, lipid profiles, blood pressure and frequencies of metabolic disorders and hypertension,” said researchers.
“Hence, we suggest that COC plus spironolactone should be considered as a valid pharmacological approach for the treatment of patients with classic PCOS not seeking fertility,” they added.